Two conserved histone demethylases regulate mitochondrial stress-induced longevity
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Across eukaryotic species, mild mitochondrial stress can have beneficial effects on the lifespan of organisms. Mitochondrial dysfunction activates an unfolded protein response (UPR(mt)), a stress signaling mechanism designed to ensure mitochondrial homeostasis. Perturbation of mitochondria during larval development in C. elegans not only delays aging but also maintains UPR(mt) signaling, suggesting an epigenetic mechanism that modulates both longevity and mitochondrial proteostasis throughout life. We identify the conserved histone lysine demethylases jmjd-1.2/PHF8 and jmjd-3.1/JMJD3 as positive regulators of lifespan in response to mitochondrial dysfunction across species. Reduction of function of the demethylases potently suppresses longevity and UPR(mt) induction, while gain of function is sufficient to extend lifespan in a UPR(mt)-dependent manner. A systems genetics approach in the BXD mouse reference population further indicates conserved roles of the mammalian orthologs in longevity and UPR(mt) signaling. These findings illustrate an evolutionary conserved epigenetic mechanism that determines the rate of aging downstream of mitochondrial perturbations.
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KDM6B/JMJD-3.1 and PHF8/JMJD-1.2 are necessary for lifespan extension induced by mitochondrial dysfunction, and overexpression of either extends lifespan in C. elegans.
“In addition, KDM6B/JMJD-3.1 and PHF8/JMJD-1.2 are necessary for lifespan extension induced by mitochondrial dysfunction, and overexpression of either of these genes extends lifespan in C. elegans (Merkwirth et al., 2016).”
From The Aging Epigenome (2016) · cites this paper as Merkwirth et al., 2016
Mice with higher PHF8/JMJD-1.2 expression are longer lived, suggesting link between PHF8 and longevity may be conserved from invertebrates to mammals.
“Interestingly, mice with higher PHF8/JMJD-1.2 expression are longer lived, suggesting that the link between PHF8/JMJD-1.2 and longevity might be conserved from invertebrates to mammals (Merkwirth et al., 2016).”
From The Aging Epigenome (2016) · cites this paper as Merkwirth et al., 2016
H3K9 and H3K27 methylation changes are important for UPRmt gene induction in C. elegans, mice, and human cells.
“changes in the methylation of H3K9 and H3K27 have recently been found to be important for the induction of genes involved in the UPRmt in C. elegans, mice, and human cells (Merkwirth et al., 2016; Tian et al., 2016).”
From The Aging Epigenome (2016) · cites this paper as Merkwirth et al., 2016
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Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Walter, P., & Ron, D. (2011) · Science · doi:10.1126/science.1209038 · Cited by 5,893 · see citing works
A C. elegans mutant that lives twice as long as wild type
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993) · Nature · doi:10.1038/366461a0 · Cited by 3,387 · see citing works
Understanding the odd science of aging
Kirkwood, T. B. L. (2005) · Cell · doi:10.1016/j.cell.2005.01.027 · Cited by 1,984 · see citing works
UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development
Agger, K., Cloos, P. A., Christensen, J. F., Pasini, D., Rose, S., Rappsilber, J., Issaeva, I., Canaani, E., Salcini, A. E., & Helin, K. (2007) · Nature · doi:10.1038/nature06145 · Cited by 1,392 · see citing works
Rates of Behavior and Aging Specified by Mitochondrial Function During Development
Dillin, A., Hsu, A.-L., Arantes-Oliveira, N., Lehrer-Graiwer, J., Hsin, H., Fraser, A. G., Kamath, R. S., Ahringer, J., & Kenyon, C. (2002) · Science · doi:10.1126/science.1077780 · Cited by 1,121 · see citing works
Self-citationThe Cell Non-Autonomous Nature of Electron Transport Chain-Mediated Longevity
Durieux, J., Wolff, S., & Dillin, A. (2011) · Cell · doi:10.1016/j.cell.2010.12.016 · Cited by 1,059 · cited 2× · see citing works
“…flies, and mice, mitochondrial dysfunction can delay the aging process (Copeland et al., 2009; Dell’agnello et al., 2007; Dillin et al., 2002b; Feng et al., 2001; Kirchman et al., 1999; Lee et al., 2003; Liu et al., 2005), but, when occurring later in life, has deleterious effects and is…”
Self-citationMitonuclear protein imbalance as a conserved longevity mechanism
Houtkooper, R. H., Mouchiroud, L., Ryu, D., Moullan, N., Katsyuba, E., Knott, G., Williams, R. W., & Auwerx, J. (2013) · Nature · doi:10.1038/nature12188 · Cited by 1,035 · see citing works
Self-citationMitochondrial Import Efficiency of ATFS-1 Regulates Mitochondrial UPR Activation
Nargund, A. M., Pellegrino, M., Fiorese, C. J., Baker, B. M., & Haynes, C. M. (2012) · Science · doi:10.1126/science.1223560 · Cited by 1,027 · see citing works
Signals from the reproductive system regulate the lifespan of C. elegans
Hsin, H., & Kenyon, C. J. (1999) · Nature · doi:10.1038/20694 · Cited by 1,015 · see citing works
A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity
Lee, S. S., Lee, R. Y. N., Fraser, A. G., Kamath, R. S., Ahringer, J., & Ruvkun, G. (2003) · Nature Genetics · doi:10.1038/ng1056 · Cited by 969 · see citing works
The genetics of caloric restriction in Caenorhabditis elegans
Lakowski, B., & Hekimi, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.13091 · Cited by 967 · see citing works
Molecular mechanisms and potential functions of histone demethylases
Kooistra, S. M., & Helin, K. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3327 · Cited by 882 · see citing works
Mitochondrial Electron Transport Is a Key Determinant of Life Span in Caenorhabditis elegans
Feng, J., Bussière, F., & Hekimi, S. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00071-5 · Cited by 675 · see citing works
Yoneda, T., Benedetti, C., Urano, F., Clark, S. G., Harding, H. P., & Ron, D. (2004) · Journal of Cell Science · doi:10.1242/jcs.01275 · Cited by 636 · see citing works
ClpP Mediates Activation of a Mitochondrial Unfolded Protein Response in C. elegans
Haynes, C. M., Petrova, K., Benedetti, C., Yang, Y., & Ron, D. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.07.016 · Cited by 595 · see citing works
XBP-1 Is a Cell-Nonautonomous Regulator of Stress Resistance and Longevity
Taylor, R. C., & Dillin, A. G. (2013) · Cell · doi:10.1016/j.cell.2013.05.042 · Cited by 570 · see citing works
Self-citationThe metabolite alpha-ketoglutarate extends lifespan by inhibiting the ATP synthase and TOR
Chin, R., Fu, X., Pai, M. Y., Vergnes, L., Hwang, H., Deng, G., Diep, S., Lomenick, B., Meli, V., Monsalve, G. C., et al. (2014) · Nature · doi:10.1038/nature13264 · Cited by 570 · see citing works
Mitochondria: The Next (Neurode)Generation
Schon, E. A., & Przedborski, S. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.003 · Cited by 568 · see citing works
Greer, E. L., Maures, T. J., Hauswirth, A. G., Green, E. M., Leeman, D. S., Maro, G. S., Han, S., Banko, M. R., Gozani, O., & Brunet, A. (2010) · Nature · doi:10.1038/nature09195 · Cited by 543 · see citing works
Aging, Rejuvenation, and Epigenetic Reprogramming: Resetting the Aging Clock
Rando, T. A., & Chang, H. Y. (2012) · Cell · doi:10.1016/j.cell.2012.01.003 · Cited by 520 · see citing works
Haynes, C. M., Yang, Y., Blais, S., Neubert, T., & Ron, D. (2010) · Molecules and Cells · doi:10.1016/j.molcel.2010.01.015 · Cited by 480 · see citing works
Timing Requirements for Insulin/IGF-1 Signaling in C. elegans
Dillin, A., Crawford, D. K., & Kenyon, C. J. (2002) · Science · doi:10.1126/science.1074240 · Cited by 467 · see citing works
Self-citationNargund, A. M., Fiorese, C. J., Pellegrino, M. W., Deng, P., & Haynes, C. M. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.008 · Cited by 463 · see citing works
PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression.
Liu, W., Tanasa, B., Tyurina, O. V., Zhou, T. Y., Gassmann, R., Liu, W. T., Ohgi, K. A., Benner, C., Garcia-Bassets, I., Aggarwal, A. K., et al. (2010) · Nature · doi:10.1038/nature09272 · Cited by 441 · see citing works
Extension of Drosophila Life Span by RNAi of the Mitochondrial Respiratory Chain
Copeland, J. M., Cho, J., Lo, T., Hur, J. H., Bahadorani, S., Arabyan, T., Rabie, J., Soh, J., & Walker, D. W. (2009) · Current Biology · doi:10.1016/j.cub.2009.08.016 · Cited by 409 · see citing works
The Heat Shock Response: Systems Biology of Proteotoxic Stress in Aging and DiseasePreprint
Morimoto, R. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2012.76.010637 · Cited by 407 · see citing works
Muscle Mitohormesis Promotes Longevity via Systemic Repression of Insulin Signaling
Owusu-Ansah, E., Song, W., & Perrimon, N. (2013) · Cell · doi:10.1016/j.cell.2013.09.021 · Cited by 395 · see citing works
Rea, S. L., Ventura, N., & Johnson, T. E. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050259 · Cited by 383 · see citing works
Benedetti, C., Haynes, C. M., Yang, Y., Harding, H. P., & Ron, D. (2006) · Genetics · doi:10.1534/genetics.106.061580 · Cited by 382 · see citing works
Mitochondrial stress induces chromatin reorganization to promote longevity and UPR(mt)
Tian, Y., Garcia, G., Bian, Q., Steffen, K. K., Joe, L., Wolff, S., Meyer, B. J., & Dillin, A. (2016) · Cell · doi:10.1016/j.cell.2016.04.011 · Cited by 370 · see citing works
Self-citationContrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia
Ntziachristos, P., Tsirigos, A., Welstead, G. G., Trimarchi, T., Bakogianni, S., Xu, L., Loizou, E., Holmfeldt, L., Strikoudis, A., King, B., et al. (2014) · Nature · doi:10.1038/nature13605 · Cited by 366 · see citing works
Liu, X., Jiang, N., Hughes, B., Bigras, E., Shoubridge, E., & Hekimi, S. (2005) · Genes & Development · doi:10.1101/gad.1352905 · Cited by 345 · see citing works
Repression of the Heat Shock Response Is a Programmed Event at the Onset of Reproduction
Labbadia, J. P., & Morimoto, R. I. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.06.027 · Cited by 330 · see citing works
Interorganelle signaling is a determinant of longevity in Saccharomyces cerevisiae
Kirchman, P. A., Kim, S., Lai, C.-Y., & Jazwinski, S. M. (1999) · Genetics · doi:10.1093/genetics/152.1.179 · Cited by 328 · see citing works
Increased longevity and refractoriness to Ca2+-dependent neurodegeneration in Surf1 knockout mice
Dell'Agnello, C., Leo, S., Agostino, A., Szabadkai, G., Tiveron, C., Zulian, A., Prelle, A., Roubertoux, P., Rizzuto, R., & Zeviani, M. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddl477 · Cited by 308 · see citing works
Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development
Qi, H. H., Sarkissian, M., Hu, G., Wang, Z., Bhattacharjee, A., Gordon, D. B., Gonzales, M., Lan, F., Ongusaha, P. P., Huarte, M., et al. (2010) · Nature · doi:10.1038/nature09261 · Cited by 303 · see citing works
Histone Methyl Transferases and Demethylases; Can They Link Metabolism and Transcription?
Teperino, R., Schoonjans, K., & Auwerx, J. H. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.09.004 · Cited by 270 · see citing works
Self-citationQuality Control of Mitochondrial ProteostasisPreprint
Baker, M. J., Tatsuta, T., & Langer, T. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a007559 · Cited by 260 · see citing works
Multilayered Genetic and Omics Dissection of Mitochondrial Activity in a Mouse Reference Population
Wu, Y., Williams, E. G., Dubuis, S., Mottis, A., Jovaisaite, V., Houten, S. M., Argmann, C. A., Faridi, P., Wolski, W., Kutalik, Z., et al. (2014) · Cell · doi:10.1016/j.cell.2014.07.039 · Cited by 244 · see citing works
Self-citationInhibition of demethylases by GSK-J1/J4
Heinemann, B., Nielsen, J. M., Hudlebusch, H. R., Lees, M. J., Larsen, D. V., Boesen, T. P., Labelle, M., Gerlach, L., Birk, P., & Helin, K. (2014) · Nature · doi:10.1038/nature13688 · Cited by 230 · see citing works
Andreux, P. A., Williams, E. G., Koutníková, H., Houtkooper, R. H., Champy, M., Henry, H., Schoonjans, K., Williams, R. W., & Auwerx, J. H. (2012) · Cell · doi:10.1016/j.cell.2012.08.012 · Cited by 224 · see citing works
Self-citationPHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation
Feng, W., Yonezawa, M., Ye, J., Jenuwein, T., & Grummt, I. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1778 · Cited by 219 · see citing works
Kleine‐Kohlbrecher, D., Christensen, J. F., Vandamme, J., Abarrategui, I., Bak, M., Tommerup, N., Shi, X., Gozani, O., Rappsilber, J., Salcini, A. E., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.03.002 · Cited by 212 · see citing works
Histone methylation makes its mark on longevity
Han, S., & Brunet, A. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.11.001 · Cited by 204 · see citing works
The MES-2/MES-3/MES-6 Complex and Regulation of Histone H3 Methylation in C. elegans
Bender, L. B., Cao, R., Zhang, Y., & Strome, S. (2004) · Current Biology · doi:10.1016/j.cub.2004.08.062 · Cited by 189 · see citing works
Mitochondrial Genome Content Is Regulated during Nematode Development
Tsang, W. Y. W., & Lemire, B. D. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2002.6394 · Cited by 187 · see citing works
Epigenetic silencing mediates mitochondria stress-induced longevity
Schroeder, E. A., Raimundo, N., & Shadel, G. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.003 · Cited by 186 · see citing works
HSF-1–mediated cytoskeletal integrity determines thermotolerance and life span
Baird, N. A., Douglas, P. M., Simic, M., Grant, A. R., Moresco, J. J., Wolff, S., Yates, J. R., Manning, G., & Dillin, A. G. (2014) · Science · doi:10.1126/science.1253168 · Cited by 181 · see citing works
Self-citationPHF8 Targets Histone Methylation and RNA Polymerase II To Activate Transcription
Fortschegger, K., de Graaf, P., Outchkourov, N. S., van Schaik, F. M. A., Timmers, H. T. M., & Shiekhattar, R. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01520-09 · Cited by 119 · see citing works
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Hipp, M. S., Kasturi, P., & Hartl, F. U. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0101-y · Cited by 1,642 · see citing works
Quirós, P. M., Prado, M. A., Zamboni, N., D’Amico, D., Williams, R. W., Finley, D., Gygi, S. P., & Auwerx, J. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201702058 · Cited by 832 · see citing works
Self-citationMetabolic Control of Longevity
López-Otín, C., Galluzzi, L., Freije, J. M. P., Madeo, F., & Kroemer, G. (2016) · Cell · doi:10.1016/j.cell.2016.07.031 · Cited by 753 · see citing works
The mitochondrial UPR: mechanisms, physiological functions and implications in ageing
Shpilka, T., & Haynes, C. M. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.110 · Cited by 716 · see citing works
Epigenetic regulation of aging: implications for interventions of aging and diseases
Kang, W., Liu, H., Hu, Q., Wang, L., Liu, J., Zheng, Z., Zhang, W., Ren, J., Zhu, F., & Liu, G. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01211-8 · Cited by 694 · see citing works
An energetic view of stress: Focus on mitochondria
Picard, M. A., McEwen, B. S., Epel, E. S., & Sandi, C. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.01.001 · Cited by 565 · see citing works
Booth, L. N., & Brunet, A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.013 · Cited by 499 · see citing works
UPRmt regulation and output: a stress response mediated by mitochondrial-nuclear communication
Melber, A., & Haynes, C. M. (2018) · Cell Research · doi:10.1038/cr.2018.16 · Cited by 488 · see citing works
The ageing epigenome and its rejuvenation
Zhang, W., Qu, J. T., Liu, G., & Belmonte, J. C. I. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0204-5 · Cited by 472 · see citing works
Picca, A., Calvani, R., Coelho‐Júnior, H. J., Landi, F., Bernabei, R., & Marzetti, E. (2020) · Antioxidants · doi:10.3390/antiox9080647 · Cited by 456 · see citing works
Cell biology of the mitochondrion
van der Bliek, A. M., Sedensky, M. M., & Morgan, P. G. (2017) · Genetics · doi:10.1534/genetics.117.300262 · Cited by 388 · see citing works
Zhu, X., Chen, Z., Shen, W., Huang, G., Sedivy, J. M., Wang, H., & Ju, Z. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00646-9 · Cited by 410 · see citing works
Mitochondrial stress induces chromatin reorganization to promote longevity and UPR(mt)
Tian, Y., Garcia, G., Bian, Q., Steffen, K. K., Joe, L., Wolff, S., Meyer, B. J., & Dillin, A. (2016) · Cell · doi:10.1016/j.cell.2016.04.011 · Cited by 370 · see citing works
Self-citationThe role of mitochondria in aging
Jang, J. Y., Blum, A., Liu, J., & Finkel, T. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120842 · Cited by 358 · see citing works
Mitochondria and Epigenetics – Crosstalk in Homeostasis and Stress
Matilainen, O., Quirós, P. M., & Auwerx, J. H. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.02.004 · Cited by 368 · see citing works
Self-citationMitochondrial dysfunction in aging
Guo, Y., Guan, T., Shafiq, K., Yu, Q., Jiao, X., Na, D., Li, M., Zhang, G., & Kong, J. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101955 · Cited by 350 · see citing works
Repairing mitochondrial dysfunction in disease
Sorrentino, V., Menzies, K. J., & Auwerx, J. (2018) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104908 · Cited by 337 · see citing works
Kim, K. H., Son, J. M., Benayoun, B. A., & Lee, C. D. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.008 · Cited by 311 · see citing works
Epigenetic changes during aging and their reprogramming potential
Kane, A. E., & Sinclair, D. A. (2019) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2019.1570075 · Cited by 283 · see citing works
Cellular and epigenetic drivers of stem cell ageing
Ermolaeva, M., Neri, F., Ori, A., & Rudolph, K. L. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0020-3 · Cited by 272 · see citing works
Rottenberg, H., & Hoek, J. B. (2017) · Aging Cell · doi:10.1111/acel.12650 · Cited by 275 · see citing works
Parkhitko, A. A., Jouandin, P., Mohr, S. E., & Perrimon, N. (2019) · Aging Cell · doi:10.1111/acel.13034 · Cited by 276 · see citing works
Forsström, S., Jackson, C. B., Carroll, C. J., Kuronen, M., Pirinen, E., Pradhan, S., Marmyleva, A., Auranen, M., Kleine, I.-M., Khan, N. A., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.019 · Cited by 252 · see citing works
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Ren, R., Ocampo, A., Liu, G., & Belmonte, J. C. I. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.019 · Cited by 269 · see citing works
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Zhang, Q., Wu, X., Chen, P., Liu, L., Xin, N., Tian, Y., & Dillin, A. G. (2018) · Cell · doi:10.1016/j.cell.2018.06.029 · Cited by 255 · see citing works
Self-citationNeuroendocrine Coordination of Mitochondrial Stress Signaling and Proteostasis
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Self-citationPleiotropic effects of mitochondria in aging
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Self-citationByun, S., Seok, S., Kim, Y., Zhang, Y., Yau, P. M., Iwamori, N., Xu, H. E., Ma, J., KEMPER, B. W., & Kemper, J. K. (2020) · Nature Communications · doi:10.1038/s41467-020-14384-z · Cited by 220 · see citing works
Zinovkin, R. A., & Zamyatnin, A. A. (2019) · Current Molecular Pharmacology · doi:10.2174/1874467212666181127151059 · Cited by 209 · see citing works
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Lyu, G., Guan, Y., Zhang, C., Zong, L., Sun, L., Huang, X., Huang, L., Zhang, L., Tian, X., Zhou, Z., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04994-z · Cited by 176 · see citing works
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Self-citationCellular proteostasis decline in human senescence
Sabath, N., Levy‐Adam, F., Younis, A., Rozales, K., Meller, A., Hadar, S., Soueid‐Baumgarten, S., & Shalgi, R. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2018138117 · Cited by 148 · see citing works
Maria Jose Perez, J., Ivanyuk, D., Panagiotakopoulou, V., Napoli, G. D., Kalb, S., Brunetti, D., Al‐Shaana, R., Kaeser, S. A., Fraschka, S. A. K., Jucker, M., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0807-4 · Cited by 146 · see citing works
Methylation across the central dogma in health and diseases: new therapeutic strategies
Liu, R., Zhao, E., Yu, H., Yuan, C., Abbas, M. N., & Cui, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01528-y · Cited by 147 · see citing works
The mitochondrial unfolded protein response: Signaling from the powerhouse
Qureshi, M. A., Haynes, C. M., & Pellegrino, M. W. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.791061 · Cited by 142 · see citing works
Cardamone, M. D., Tanasă, B., Cederquist, C., Huang, J., Mahdaviani, K., Li, W., Rosenfeld, M. G., Liesa, M., & Perissi, V. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.01.037 · Cited by 134 · see citing works
Mitochondrial complex I as a therapeutic target for Alzheimer's disease
Trushina, E. V., Trushin, S., & Hasan, M. F. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.11.003 · Cited by 130 · see citing works
Mitohormesis in Mice via Sustained Basal Activation of Mitochondrial and Antioxidant Signaling
Cox, C. S., McKay, S. E., Holmbeck, M. A., Christian, B. E., Scortea, A. C., Tsay, A. J., Newman, L. E., & Shadel, G. S. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.07.011 · Cited by 121 · see citing works
JMJD3 in the regulation of human diseases
Zhang, X., Liu, L., Yuan, X., Wei, Y., & Wei, X. (2019) · Protein & Cell · doi:10.1007/s13238-019-0653-9 · Cited by 121 · see citing works
Matai, L., Sarkar, G. C., Chamoli, M., Malik, Y., Kumar, R., Rautela, U., Jana, N. R., Chakraborty, K., & Mukhopadhyay, A. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900055116 · Cited by 120 · see citing works
Mitochondria as intracellular signaling platforms in health and disease
Tan, J. X., & Finkel, T. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.202002179 · Cited by 119 · see citing works
Repressive Chromatin in Caenorhabditis elegans: Establishment, Composition, and Function
Ahringer, J., & Gasser, S. M. (2018) · Genetics · doi:10.1534/genetics.117.300386 · Cited by 112 · see citing works
Two genomes, one cell: Mitochondrial-nuclear coordination via epigenetic pathways
Wiese, M., & Bannister, A. J. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.006 · Cited by 116 · see citing works
Two conserved epigenetic regulators prevent healthy ageing
Yuan, J., Chang, S., Yin, S., Liu, Z.-Y., Cheng, X., Liu, X., Jiang, Q., Gao, G., Lin, D.-Y., Kang, X.-L., et al. (2020) · Nature · doi:10.1038/s41586-020-2037-y · Cited by 111 · see citing works
Zhu, D., Wu, X., Zhou, J., Li, X., Huang, X., Li, J., Wu, J., Bian, Q., Wang, Y., & Tian, Y. (2020) · Science Advances · doi:10.1126/sciadv.abb2529 · Cited by 112 · see citing works
Cytosolic Proteostasis Networks of the Mitochondrial Stress Response
D'Amico, D. F., Sorrentino, V., & Auwerx, J. H. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.05.002 · Cited by 106 · see citing works
Self-citationGenomic Instability and Epigenetic Changes during Aging
López-Gil, L., Pascual‐Ahuir, A., & Proft, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241814279 · Cited by 120 · see citing works
Histone deacetylase HDA-1 modulates mitochondrial stress response and longevity
Shao, L.-W., Peng, Q., Dong, M., Gao, K., Li, Y., Li, Y., Li, C., & Liu, Y. (2020) · Nature Communications · doi:10.1038/s41467-020-18501-w · Cited by 107 · see citing works
Cribbs, A. P., Terlecki-Zaniewicz, S., Philpott, M., Baardman, J., Ahern, D., Lindow, M., Obad, S., Oerum, H., Sampey, B. P., Mander, P. K., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1919893117 · Cited by 99 · see citing works
Zhang, Q., Wang, Z., Zhang, W., Wen, Q., Li, X., Zhou, J., Wu, X., Guo, Y., Liu, Y., Wei, C., et al. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00724-8 · Cited by 101 · see citing works
Wan, Q.-L., Meng, X., Wang, C., Dai, W., Luo, Z., Yin, Z., Ju, Z., Fu, X., Yang, J., Ye, Q., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28469-4 · Cited by 102 · see citing works
Integrating the Hallmarks of Aging Throughout the Tree of Life: A Focus on Mitochondrial Dysfunction
van der Rijt, S., Molenaars, M., McIntyre, R. L., Janssens, G. E., & Houtkooper, R. H. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.594416 · Cited by 97 · see citing works
How the Mitoprotein-Induced Stress Response Safeguards the Cytosol: A Unified View
Boos, F., Labbadia, J. P., & Herrmann, J. M. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.12.003 · Cited by 90 · see citing works
Generation and Release of Mitochondrial-Derived Vesicles in Health, Aging and Disease
Picca, A., Guerra, F., Calvani, R., Coelho‐Júnior, H. J., Bossola, M., Landi, F., Bernabei, R., Bucci, C., & Marzetti, E. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9051440 · Cited by 98 · see citing works
Sensing, signaling and surviving mitochondrial stress
Eckl, E.-M., Ziegemann, O., Krumwiede, L., Fessler, E., & Jae, L. T. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03887-7 · Cited by 93 · see citing works
Mitohormesis Primes Tumor Invasion and Metastasis
Kenny, T. C., Craig, A. J., Villanueva, A., & Germain, D. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.095 · Cited by 96 · see citing works
Zhou, Z., Fan, Y., Zong, R., & Tan, K. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101702 · Cited by 99 · see citing works
The mitochondrial permeability transition: Nexus of aging, disease and longevity
Rottenberg, H., & Hoek, J. B. (2021) · Cells · doi:10.3390/cells10010079 · Cited by 94 · see citing works
“Similar to deacetylases, Histone Demethylases also contribute to stress-induced protection (106).”
BackgroundProtein trafficking at the crossroads to mitochondria
Wasilewski, M., Chojnacka, K., & Chacińska, A. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.10.019 · Cited by 89 · see citing works
Mitophagy-driven mitochondrial rejuvenation regulates stem cell fate
Vázquez‐Martín, A., den Haute, C. V., Cufí, S., Corominas-Faja, B., Cuyàs, E., López‐Bonet, E., Rodríguez‐Gallego, E., Fernández‐Arroyo, S., Joven, J., Baekelandt, V., et al. (2016) · Aging · doi:10.18632/aging.100976 · Cited by 88 · see citing works
Mitochondrial stress management: a dynamic journey
Valera‐Alberni, M., & Cantó, C. (2018) · Cell Stress · doi:10.15698/cst2018.10.158 · Cited by 90 · see citing works
Systemic effects of mitochondrial stress
Bar‐Ziv, R., Bolas, T., & Dillin, A. G. (2020) · EMBO Reports · doi:10.15252/embr.202050094 · Cited by 83 · see citing works
Self-citationSeok, S., Kim, Y., Byun, S., Choi, S., Xiao, Z., Iwamori, N., Zhang, Y., Wang, C., Ma, J., Ge, K., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97736 · Cited by 86 · see citing works
Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion
Liu, Y. J., Janssens, G. E., McIntyre, R. L., Molenaars, M., Kamble, R., Gao, A. W., Jongejan, A., van Weeghel, M., MacInnes, A. W., & Houtkooper, R. H. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1007633 · Cited by 80 · see citing works
Mitochondrial Quality Control Mechanisms and the PHB (Prohibitin) Complex
Hernando‐Rodríguez, B., & Artal‐Sanz, M. (2018) · Cells · doi:10.3390/cells7120238 · Cited by 83 · see citing works
Denzel, M. S., Lapierre, L. R., & Mack, H. I. D. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.08.001 · Cited by 81 · see citing works
Li, T. Y., Sleiman, M. B., Li, H., Gao, A. W., Mottis, A., Bachmann, A. M., Alam, G. E., Li, X., Goeminne, L. J. E., Schoonjans, K., et al. (2021) · Nature Aging · doi:10.1038/s43587-020-00025-z · Cited by 78 · see citing works
Self-citationMitochondrial chaperone HSP‐60 regulates anti‐bacterial immunity via p38 MAP kinase signaling
Jeong, D., Lee, D.-Y., Hwang, S., Lee, Y., Lee, J., Seo, M., Hwang, W., Seo, K., Hwang, A. B., Artan, M., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201694781 · Cited by 77 · see citing works
UPR ER promotes lipophagy independent of chaperones to extend life span
Daniele, J. R., Higuchi‐Sanabria, R., Durieux, J., Monshietehadi, S., Ramachandran, V., Tronnes, S. U., Kelet, N., Sanchez, M., Metcalf, M. G., Garcia, G., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz1441 · Cited by 78 · see citing works
Self-citationUpdating the Free Radical Theory of Aging
Ziada, A. S., Smith, M.-S. R., & Côté, H. C. F. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.575645 · Cited by 80 · see citing works
Aging: All roads lead to mitochondria
Son, J. M., & Lee, C. D. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.02.006 · Cited by 82 · see citing works
Wan, Q.-L., Meng, X., Dai, W., Luo, Z., Wang, C., Fu, X., Yang, J., Ye, Q., & Zhou, Q. (2021) · Science Advances · doi:10.1126/sciadv.abc3026 · Cited by 78 · see citing works
Interaction between epigenetic and metabolism in aging stem cells
Brunet, A., & Rando, T. A. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2016.12.009 · Cited by 76 · see citing works
Katiyar, A., Fujimoto, M., Tan, K., Kurashima, A., Srivastava, P., Okada, M., Takii, R., & Nakai, A. (2020) · FEBS Open Bio · doi:10.1002/2211-5463.12863 · Cited by 72 · see citing works
Mohrin, M., Widjaja, A., Liu, Y., Luo, H., & Chen, D. (2018) · Aging Cell · doi:10.1111/acel.12756 · Cited by 76 · see citing works
Genetic variation in glia–neuron signalling modulates ageing rate
Yin, J., Gao, G., Liu, X., Hao, Z.-Q., Li, K., Kang, X.-L., Li, H., Shan, Y., Hu, W., Li, H., et al. (2017) · Nature · doi:10.1038/nature24463 · Cited by 73 · see citing works
The virtuous cycle of human genetics and mouse models in drug discovery
Nadeau, J. H., & Auwerx, J. H. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0009-9 · Cited by 71 · see citing works
Self-citationTranslational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity
Lan, J., Rollins, J. A., Zang, X., Wu, D., Zou, L., Wang, Z., Ye, C., Wu, Z., Kapahi, P., Rogers, A. N., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.078 · Cited by 73 · see citing works
Zhou, L., He, B., Deng, J., Pang, S., & Tang, H. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1008122 · Cited by 71 · see citing works
Tran, H. C., & Aken, O. V. (2020) · Mitochondrion · doi:10.1016/j.mito.2020.05.009 · Cited by 69 · see citing works
Wodrich, A. P. K., Scott, A. W., Shukla, A. K., Harris, B. T., & Giniger, E. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.831116 · Cited by 67 · see citing works
Systems Phytohormone Responses to Mitochondrial Proteotoxic Stress
Wang, X., & Auwerx, J. H. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.006 · Cited by 70 · see citing works
Self-citationYing, Z., Xiang, G., Zheng, L., Tang, H., Duan, L., Lin, X., Zhao, Q., Chen, K., Wu, Y., Xing, G., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.08.001 · Cited by 69 · see citing works
Organismal Protein Homeostasis Mechanisms
Hoppe, T., & Cohen, E. (2020) · Genetics · doi:10.1534/genetics.120.301283 · Cited by 65 · see citing works
The UPRmt preserves mitochondrial import to extend lifespan
Xin, N., Durieux, J., Yang, C., Wolff, S., Kim, H.-E., & Dillin, A. G. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202201071 · Cited by 67 · see citing works
Self-citationIntegrating the UPRmtinto the mitochondrial maintenance network
Fiorese, C. J., & Haynes, C. M. (2017) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2017.1291577 · Cited by 66 · see citing works
Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets
Dobson, A. J., Ezcurra, M., Flanagan, C. E., Summerfield, A. C., Piper, M. D. W., Gems, D., & Alic, N. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.029 · Cited by 63 · see citing works
The role of epigenetics in the development of obesity
Obri, A., Serra, D., Herrero, L., & Mera, P. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.113973 · Cited by 65 · see citing works
Mitochondrial unfolded protein response (UPRmt): what we know thus far
Torres, A. K., Fleischhart, V., & Inestrosa, N. C. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1405393 · Cited by 65 · see citing works
Kim, S., & Sieburth, D. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.037 · Cited by 65 · see citing works
Sensing the Stress: A Role for the UPRmt and UPRam in the Quality Control of Mitochondria
Callegari, S., & Dennerlein, S. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00031 · Cited by 58 · see citing works
Cancer cell metabolism: Rewiring the mitochondrial hub
Oliveira, G. L., Coelho, A. R., Marques, R., & Oliveira, P. J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.166016 · Cited by 62 · see citing works
- Authors
- Merkwirth, C., Jovaisaite, V., Durieux, J., Matilainen, O., Jordan, S. D., Quiros, P. M., Steffen, K. K., Williams, E. G., Mouchiroud, L., Tronnes, S. U., Murillo, V., Wolff, S. C., Shaw, R. J., Auwerx, J., & Dillin, A.
- Affiliations
- Salk Institute for Biological Studies (US)
- École Polytechnique Fédérale de Lausanne (CH)
- Howard Hughes Medical Institute (US)
- Scripps Research Institute (US)
- Corresponding author
- Auwerx, Johan
- Dillin, Andrew
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 165
- Issue
- 5
- Pages
- 1209-1223
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4889222
- OpenAlex
- W2343257250
- Cited by
- 363
- References
- 51
- Citations by year
- 2026: 28 · 2025: 20 · 2024: 42 · 2023: 26 · 2022: 43 · 2021: 44 · 2020: 42 · 2019: 34 · 2018: 38 · 2017: 35 · 2016: 11
- FWCI
- 21.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Howard Hughes Medical Institute (P40 OD010440, R01 ES021667)
- American Heart Association (15POST22510020)
- Glenn Foundation for Medical Research
- École Polytechnique Fédérale de Lausanne
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (140780)
- National Institutes of Health (OD010440, P40OD010440)
- National Institute on Aging (R01AG043930)
- National Cancer Institute (P30CA014195)
- National Institute of Environmental Health Sciences (R01ES021667)
- National Center for Research Resources (S10RR029668, S10RR027303)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- histone lysine demethylases, mitochondrial stress, unfolded protein response, longevity, lifespan extension, mitochondrial proteostasis, Caenorhabditis elegans, evolutionary conservation
- MeSH terms
- Animals, Longevity, Mitochondria, Transcription Factors, Transcription, Genetic, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Mice, Histone Demethylases, Jumonji Domain-Containing Histone Demethylases, Unfolded Protein Response
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